PMID- 20375081
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20141120
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 116
IP  - 1
DP  - 2010 Jul
TI  - Assessment of chemical skin-sensitizing potency by an in vitro assay based on 
      human dendritic cells.
PG  - 122-9
LID - 10.1093/toxsci/kfq108 [doi]
AB  - The skin-sensitizing potential of chemicals is an important concern for public 
      health and thus a significant end point in the hazard identification process. To 
      determine skin-sensitizing capacity, large research efforts focus on the 
      development of assays, which do not require animals. As such, an in vitro test 
      has previously been developed based on the differential expression of CREM and 
      CCR2 transcripts in CD34(+) progenitor-derived dendritic cells (CD34-DC), which 
      allows to classify chemicals as skin (non-)sensitizing. However, skin 
      sensitization is not an all-or-none phenomenon, and up to now, the assessment of 
      relative potency can only be derived using the in vivo local lymph node assay 
      (LLNA). In our study, we analyzed the feasibility to predict the sensitizing 
      potency, i.e., the LLNA EC3 values, of 15 skin sensitizers using in vitro data 
      from the CD34-DC-based assay. Hereto, we extended the in vitro-generated gene 
      expression data set by an additional source of information, the concentration of 
      the compound that causes 20% cell damage (IC20) in CD34-DC. We statistically 
      confirmed that this IC20 is linearly independent from the gene expression changes 
      but that it does correlate with LLNA EC3 values. In a further analysis, we 
      applied a robust linear regression with both IC20 and expression changes of CREM 
      and CCR2 as explanatory variables. For 13 out of 15 compounds, a high linear 
      correlation was established between the in vitro model and the LLNA EC3 values 
      over a range of four orders of magnitude, i.e., from weak to extreme sensitizers.
FAU - Lambrechts, Nathalie
AU  - Lambrechts N
AD  - Unit Environmental Risk and Health, Toxicology, Flemish Institute for 
      Technological Research (VITO NV), Mol, Belgium. nathalie.lambrechts@vito.be
FAU - Vanheel, Hanne
AU  - Vanheel H
FAU - Nelissen, Inge
AU  - Nelissen I
FAU - Witters, Hilda
AU  - Witters H
FAU - Van Den Heuvel, Rosette
AU  - Van Den Heuvel R
FAU - Van Tendeloo, Viggo
AU  - Van Tendeloo V
FAU - Schoeters, Greet
AU  - Schoeters G
FAU - Hooyberghs, Jef
AU  - Hooyberghs J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100407
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
SB  - IM
MH  - Dendritic Cells/*drug effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin/cytology/*drug effects
MH  - *Toxicity Tests
EDAT- 2010/04/09 06:00
MHDA- 2010/10/22 06:00
CRDT- 2010/04/09 06:00
PHST- 2010/04/09 06:00 [entrez]
PHST- 2010/04/09 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
AID - kfq108 [pii]
AID - 10.1093/toxsci/kfq108 [doi]
PST - ppublish
SO  - Toxicol Sci. 2010 Jul;116(1):122-9. doi: 10.1093/toxsci/kfq108. Epub 2010 Apr 7.